1. Field of the Invention
This invention relates to arabinogalactans. In particular, this invention relates to an acid-modified arabinogalactan protein composition, having an arabinose:galactose ratio of less than 3.5:1 or less than 80% of the arabinose:galactose ratio of the arabinogalactan protein component of the composition prior to acid modification, prepared from Astragalus membranaceus, especially from the roots of Astragalus membranaceus. 
2. Description of Related Art
Huang-qi, Radix Astragali, is the dried root of Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge. (Fabaceae). Huang-qi is a very old and well known drug in traditional Chinese medicine. It is officially listed in the Chinese Pharmacopoeia and used mainly as a tonic and for treatment of nephritis and diabetes. It is commonly used as a decoction or “tea” alone or with other plants in the traditional medicines Shi-ka-ron (a combination with herbs Lithosperium erythrorhizon and Ligusticum wallachii) and Ren-shen-yang-rong-tang (a combination of twelve herbs including Radix Astragali) [The section entitled “Astragalus membranaceus (Fisch.) Bge.”, Section 26, pages 191–197, of “Chinese Drugs of Plant Origin”, W. Tang and G. Eisenbrand, eds., Springer Verlag, Berlin, 1992].
Huang-qi decoctions, and solutions prepared from the alcohol-precipitated decoction, have also been administered by injection, and are reported to give improvement in the symptoms of gastric and duodenal ulcers and increase the white blood cell count in chronic leukopenia [The section entitled “Huangqi”, pages 1041–1046, of “Pharmacology and Applications of Chinese Materia Medica”, H.-M. Chang and P. P.-H. But, eds., World Scientific Publishing Co., Singapore, 1987]. Huang-qi decoctions, purified low molecular weight fractions (e.g. 25,000–35,000 MW), and decoctions of herb mixtures containing huang-qi, have also shown activity in restoring the immune system in local xenogeneic graft-versus-host reaction [D.-T. Chu et al., “Immunotherapy with Chinese medicinal herbs. I. . . . ”, J. Clin. Lab. Immunol., 25, 119–123 (1988)], reversing cyclophosphamide-induced immune suppression [D.-T. Chu et al., “Immunotherapy with Chinese medicinal herbs. II . . . ”, J. Clin. Lab. Immunol., 25, 125–129 (1988)], potentiating LAK cell cytotoxicity generated by rIL-2 [D.-T. Chu et al., “Fractionated extract of Astragalus membranaceus.”, J. Clin. Lab. Immunol., 25, 183–187 (1988)], enhancing the immune response in immunodepressed mice [K. S. Zhao et al., “Enhancement of the immune response in mice by Astragalus membranaceus extracts”, Immunopharmacology, 20, 225–234 (1990)], stimulating responses in mononuclear cells [Y. Sun et al., “Preliminary observations on the effects of the Chinese medicinal herbs . . . ”, J. Biol. Response Modifiers, 2, 227–237 (1983)], and stimulating bone marrow hematopoiesis in mice [M. Rou et al., “The effect of radix astragali on mouse marrow hemopoiesis”, J. Trad. Chin. Med., 3(3), 199–204 (1983); S.-I. Miura et al., “Effect of a traditional Chinese herbal medicine . . . ”, Int. J Immunopharmacol., 7(11), 771–780 (1989); and Y. Ohnishi et al., “Effects of Juzen-taiho-toh (TJ-48) . . . ”, Exp. Hematol., 18, 18–22 (1990)].
Liu, U.S. Pat. No. 4,843,067, discloses a pharmaceutical composition containing polysaccharides of huang-qi (stated to be extractable from either Astragalus membranaceus Bge. or Astragahis gummifer Labillard) and polysaccharides of dankuei. The huang-qi polysaccharides are stated to be extractable by water extraction of a powder of the roots and ethanol precipitation. Verbiscar, U.S. Pat. No. 5,2868,467, discloses immunomodulatory polysaccharide fractions from the plants of Astragalus tragacantha (tragacanth), prepared at low temperature to “maintain the integrity of the polysaccharide toward chemical and conformational changes”. Josephson et al., U.S. Pat. No. 5,336,506, discloses the use of plant polysaccharides such as arabinogalactans (isolated from larch, Larix occidentalis) and mannans to form complexes with therapeutic agents for the targeting of the therapeutic agent to a cell receptor capable of receptor-mediated endocytosis. Adams et al., U.S. Pat. No. 5,116,969, discloses an ultrarefined arabinogalactan product said to be suitable for use in density gradient separation. Jung et al., U.S. Pat. No. 5,478,576, discloses purified arabinogalactans (also from Larix occidentalis), degradative products, and modifications thereof, also for use in delivering therapeutic agents to cell receptors capable of receptor-mediated endocytosis. Lewis, U.S. Pat. No. 5,589,591, discloses endotoxin-free polysaccharides, such as arabinogalactans, dextrans, mannans, and gum arabic, prepared from impure forms of these polysaccharides by ultrafiltration through first through a low molecular weight cutoff membrane, keeping the retentate, and then through a high molecular weight cutoff membrane, keeping the filtrate.
Each of these references, however, devotes its attention to the polysaccharides (e.g. arabinogalactans) present in the products, and may even use techniques designed to exclude arabinogalactan proteins.
Arabinogalactan proteins are also found in flowering plants, and are widely distributed in most higher plants. Arabinogalactan proteins (AGPs), sometimes referred to as arabinogalactan peptides, are glycosylated proteins containing high proportions of carbohydrate and usually a low (less than 10%) protein content, although AGPs having a higher protein content are known. Among the hydroxyproline-rich glycoproteins isolatable from plants, AGPs are characterized by their generally low protein content and their general ability to bind the β-glucosyl Yariv reagent, 1,3,5-tris(4-β-D-glucopyranosyloxyphenylazo)-2,4,6-trihydroxybenzene, [J. H. Yariv et al., Biochem. J., 85, 383–388 (1962); R. L. Anderson et al., Aust. J. Plant Physiol., 4, 143–158 (1977)]. AGPs are components of gum arabic, a gummy exudate from the acacia tree, Acacia senegal, that is frequently used in food products as an emulsifier, crystallization preventer, and flavor eincapsulator. The isolation of plant AGP genes from Nicotiana alata, Nicotiana plumbaginafolia, and Pyrus communis is disclosed in Chen et al., U.S. Pat. No. 5,646,029. An extensive discussion of AGPs may be found in E. A. Nothnagel, “Proteoglycans and related components in plant cells”, Int. Rev. Cytology, 174, 195–291 (1997).
The disclosures of these and other documents referred to throughout this application are incorporated herein by reference.